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El análisis integrómico de la variación genética y la expresión génica identifica redes para los fenotipos de

Chen Yao¹, Brian H Chen¹, Roby Joehanes¹

¹From the National Heart, Lung, and Blood Institute's Framingham Heart Study, National Institutes of Health, Bethesda, MD (C.Y., B.H.C., R.J., X.Z., C.L., T.H., L.A.C., C.S.F., P.C., C.J.O'D., D.L.); Population Sciences Branch, National Institutes of Health, National Heart, Lung, and Blood Institute, Bethesda, MD (C.Y., B.H.C., R.J., X.Z., C.L., T.H., P.C., D.L.); Mathematical and Statistical Computing Laboratory, Center for Information Technology, National Institutes of Health, Bethesda, MD (R.J., P.J.M.); Department of Computer Engineering, Middle East Technical University, Ankara, Turkey (B.O.); Department of Computer Engineering, Bilkent University, Ankara, Turkey (O.T.); Department of Biostatistics, Boston University School of Public Health, Boston, MA (L.A.C.); Harvard Medical School, Boston, MA (J.B.M.); Division of Endocrinology, Metabolism, and Diabetes, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (C.S.F.); Department of Medicine, University of Massachusetts Medical School, Worchester (J.E.F.); Division of Cardiology, Massachusetts General Hospital, Boston, MA (C.J.O'D.); and Departments of Statistics and of Biostatistics and Medical Informatics, University of Wisconsin-Madison (S.K.).

|December 24, 2014

Resumen

Los investigadores crearon una red de enfermedades cardiovasculares (ECV) que vincula las variantes genéticas (SNP) a los rasgos. Esta red identificó cambios en la expresión génica que influyen en los factores de riesgo de ECV, ofreciendo posibles objetivos farmacológicos.

Área de la Ciencia:

Genética La genética.
Medicina Cardiovascular La medicina cardiovascular es una especialidad de la salud.
Biología de Sistemas Biología de Sistemas.

Sus antecedentes:

Las enfermedades cardiovasculares (ECV) implican rasgos complejos, con muchos polimorfismos de nucleótido único (SNP) asociados identificados, pero sus roles funcionales no están claros.
Los estudios de asociación de todo el genoma (GWAS) han relacionado numerosos SNPs con ECV, pero comprender su contribución a los mecanismos de la enfermedad sigue siendo un desafío.

Objetivo del estudio:

Construir una red integral que integre variantes genéticas (SNP) con diversos rasgos de enfermedades cardiovasculares (ECV).
Explorar la relación entre los SNPs y la expresión génica, y su asociación con los factores de riesgo de ECV.
Identificar posibles dianas terapéuticas para la enfermedad cardiovascular mediante el análisis de redes de expresión génica SNP.

Principales métodos:

Se construyó una red de CVD utilizando 1512 SNPs asociados con 21 rasgos de CVD de GWAS.
Se analizaron los datos de expresión génica de sangre entera de 5257 participantes del Estudio del Corazón de Framingham en relación con estos SNPs.
Se identificaron los loci de rasgos cuantitativos de expresión (eQTL), y se examinó su asociación con los factores de riesgo de ECV (lípidos, presión arterial, IMC, glucosa).

Principales resultados:

Se construyó una red de 1512 SNPs y 21 rasgos CVD, revelando conexiones entre rasgos.
Se identificaron 370 cis-eQTL y 44 trans-eQTL, formando 13 módulos relacionados con el CVD.
La expresión génica eQTL se asoció significativamente con los factores de riesgo de ECV, y el análisis de mediación sugirió que los SNPs influyen en los fenotipos a través de la expresión génica eQTL.

Conclusiones:

Un enfoque de red integró con éxito los datos de fenotipo y transcripción de SNP para CVD.
Las vías biológicas identificadas y las redes de expresión génica ofrecen información sobre posibles objetivos farmacológicos para la prevención y el tratamiento de las ECV.

Palabras clave:

enfermedades cardiovasculares enfermedad cardiovascular.Expresión génica / red de regulación de la expresión génica.variación genética variación genética.

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